Gonadotropinsarepituitaryhormones,whichareluteinizinghormoneandfollicle-stimulatinghormone.Thesehormonesareheterodimersthatconsistofacommonα subunitandauniqueβ subunit(see ).Theurineofpostmenopausalwomenisanexcellentsourceofgonadotropinsbecausepostmenopausalserumgonadotropinlevelsarehighasaresultofthelossofnegativefeedbackbyovariansteroids(see ),andthehormonesarefilteredandexcretedasintactmoleculesinurine.Athirdgonadotropinistheplacentalhormonehumanchorionicgonadotropin(hCG;see ),whichhasthesamecommonα subunitandanhCG-specificβ subunit.Itisanextremelystablehormone,andbloodhCGlevelsdoubleevery2daysduringthefirsttrimester.Accordingly,urinarylevelsofhCGalsoincreaserapidly.Pregnancy tests arebasedonimmunologicaldetectioninurineofthehCGspecificβ subunitaspartoftheintacthCGheterodimer.
Steroid hormones are synthesized by a series of enzymatic modifications of cholesterol, and a cyclopentanoperhydrophenanthrene ring (or a derivative thereof) serves as their core (
Fig. 38.8 ). The enzymatic modifications of cholesterol are of three general types: hydroxylation, dehydrogenation/ reduction, and lyase reactions. The purpose of these modifications is to produce a cholesterol derivative that is sufficiently unique to be recognized by a specific receptor. Thus progestins bind to the progesterone receptor, mineralocorticoids bind to the mineralocorticoid receptor, glucocorticoids bind to the glucocorticoid receptor, androgens bind to the androgen receptor, estrogens bind to the estrogen receptor, and the active vitamin D metabolite binds to the vitamin D receptor. The complexity of steroid hormone action is increased by the expression of multiple forms of each receptor. In addition, there is some degree of nonspecificity between steroid hormones and the receptors to which they bind. For example, glucocorticoids bind to the mineralocorticoid receptor with high affinity, and progestins, glucocorticoids, and androgens can all interact with the progesterone, glucocorticoid, and androgen receptors to some degree. As discussed later, steroid hormones are hydrophobic and pass through cell membranes easily. Accordingly, classic steroid hormone receptors are localized intracellularly and act by regulating gene expression. There is mounting evidence of the presence of plasma membrane and juxtamembrane steroid hormone receptors that mediate rapid, nongenomic actions of steroid hormones.
Steroidogenic cell types are defined as cells that can convert cholesterol to pregnenolone, which is the first reaction common to all steroidogenic pathways. Steroidogenic cells have some capacity for cholesterol synthesis but often obtain cholesterol from cholesterol-rich lipoproteins (low-density lipoproteins and high-density lipoproteins). Pregnenolone is then further modified by several enzymatic reactions. Because of their hydrophobic nature, steroid hormones and precursors can leave the steroidogenic cell easily and thus are not stored. Therefore, steroidogenesis is regulated at the level of uptake, storage, and mobilization of cholesterol and at the level of steroidogenic enzyme gene expression and activity. Steroids are not regulated at the •Fig. 38.8 A, Structureofcholesterol,theprecursorofsteroidhormones.B, Structureofsteroidhormones.